To evaluate the effect of ultrasound-guided quadratus lumborum block (QLB) preemptive analgesia on recovery in colon cancer patients undergoing open radical surgery and provide reference for its clinical application.From July 2019 to June 2020, according to the anesthesia method, 56 patients who received open radical colon surgery were divided into two groups: Group Q (n=27), which received QLB combined general anesthesia, and Group C (n=29), which received general anesthesia only. Both groups were given self-controlled intravenous analgesia pump after surgery. The primary outcome is a series of parameters representing postoperative recovery. The secondary outcome was VAS scores and opioid consumption.The first time of getting up, flatus, taking semi-liquid diet and the postoperative hospital stay in Group Q were significantly reduced (P<0.01). The rest and active VAS scores were significantly lower in Group Q (P<0.01). The opioids consumption was significantly decreased in Group Q (P<0.05).The application of ultrasound-guided QLB preemptive analgesia in open radical colon cancer surgery can significantly enhance the postoperative analgesia effect, reduce opioid consumption, and accelerate the postoperative recovery of the patients.The Chinese Clinical Trial Registry (ChiCTR-2000034824).
Hepatocellular carcinoma (HCC) is the most commonly diagnosed carcinoma and one of the leading causes of cancer-related deaths worldwide. Situs inversus totalis (SIT) is a congenital condition where in the internal organs of the abdomen and thorax lie in mirror images of their normal position. Thus far, there are very few reports on cases of SIT coexisting with HCC. Our case series is probably the largest series in world literature. The cohort of this retrospective study included a total of nine patients diagnosed with SIT-HCC and treated in our hospital between January 2013 and May 2018. Clinical characteristics, prognostic factors, and outcomes were summarized. Treatment strategies included surgery, transarterial chemoembolization, and microwave ablation. The diagnosis and treatment of patients with SIT are challenging because of organ reversion. The current treatment strategies for different stages of liver cancer are safe and feasible for patients with SIT-HCC.
Abstract The transient receptor potential cation channel subfamily M member-3 (TRPM3) channel is a recently recognized noxious heat sensor that is involved in inflammatory thermal hyperalgesia. To examine its involvement in the development of hyperalgesia in interstitial cystitis/painful bladder syndrome (IC/PBS), rats with cyclophosphamide (CYP)-induced chronic cystitis were used as a model of IC/PBS. Mechanical and thermal hyperalgesia in lower abdominal region overlying the bladder in CYP rats were measured using von Frey filaments and radiant heat, respectively. Transient receptor potential cation channel subfamily M member-3 expression at the mRNA, protein, and functional levels in dorsal root ganglion neurons innervating the bladder was detected using RNA in situ hybridization (RNAscope), Western blotting, immunohistochemistry, and Ca 2+ imaging, respectively. Transient receptor potential cation channel subfamily M member-3 channels were expressed on most of the bladder primary afferent nerve terminals containing calcitonin gene–related peptide and their cell bodies in L6-S1 dorsal root ganglion. Activation of TRPM3 in the bladder wall by its specific agonist pregnenolone sulphate or CIM0216 induced spontaneous bladder pain, calcitonin gene–related peptide release, and neurogenic inflammation that was evidenced by edema, plasma extravasation, inflammatory cell accumulation, and mast cell infiltration. In CYP rats, pretreatment with the TRPM3 antagonist primidone (2 mg/kg, i.p.) significantly alleviated the mechanical and thermal hyperalgesia, bladder submucosal edema, mast cell infiltration, and bladder hyperactivity. Cyclophosphamide-induced cystitis was associated with TRPM3 upregulation at the mRNA, protein, and functional levels in bladder afferent neurons. Our results suggest that upregulation of TRPM3 channels is involved in the development of chronic pain in CYP-induced cystitis, and targeting TRPM3 may be a pharmacological strategy for treating bladder pain in IC/PBS.
The activation of the transient receptor potential ankyrin 1 (TRPA1) channel has anti-fibrotic effects in the lung and intestine. Suburothelial myofibroblasts (subu-MyoFBs), a specialized subset of fibroblasts in the bladder, are known to express TRPA1. However, the role of the TRPA1 in the development of bladder fibrosis remains elusive. In this study, we use the transforming growth factor-β1 (TGF-β1) to induce fibrotic changes in subu-MyoFBs and assess the consequences of TRPA1 activation utilizing RT-qPCR, western blotting, and immunocytochemistry. TGF-β1 stimulation increased α-SMA, collagen type I alpha 1 chain(col1A1), collagen type III (col III), and fibronectin expression, while simultaneously suppressing TRPA1 in cultured human subu-MyoFBs. The activation of TRPA1, with its specific agonist allylisothiocyanate (AITC), inhibited TGF-β1-induced fibrotic changes, and part of these inhibition effects could be reversed by the TRPA1 antagonist, HC030031, or by reducing TRPA1 expression via RNA interference. Furthermore, AITC reduced spinal cord injury-induced fibrotic bladder changes in a rat model. The increased expression of TGF-β1, α-SMA, col1A1 and col III, and fibronectin, and the downregulation of TRPA1, were also detected in the mucosa of fibrotic human bladders. These findings suggest that TRPA1 plays a pivotal role in bladder fibrosis, and the negative cross talk between TRPA1 and TGF-β1 signaling may represent one of the mechanisms underlying fibrotic bladder lesions.
Voting is a way to aggregate individual voters' preferences. Traditionally a voter's preference is represented by a total order on the set of candidates. However, sometimes one may not have complete information about a voter's preference, and in this case, can only model a voter's preference as a partial order. Given this framework, there has been work on computing the possible and necessary winners of a (partial) profile. In this paper, we take a step further, look at sets of questions to ask in order to determine the outcome of such a partial profile. Specifically, we call a set of questions a deciding set for a candidate if the outcome of the vote for the candidate is determined no matter how the questions are answered by the voters, and a possible winning (losing) set if there is a way to answer these questions to make the candidate a winner (loser) of the vote. We discuss some interesting properties about these sets of queries, prove some complexity results about them under some well-known voting rules such as plurality and Borda, and consider their application in vote elicitation.
Aim: CYP1A2, a constitutive enzyme expressed in the liver, is among the phase I enzymes responsible for polycyclic aromatic hydrocarbons metabolism. Phenacetin O-de-ethylation is a marker for CYP1A2 activity. This study investiagtes the metabolism of phenacetin in patients with hepatocellular carcinoma (HCC). Methods: The phenacetin test was performed in 56 normal subjects and 92 HCC patients. The test was repeated in HCC patients after treatment with transcatheter arterial chemoembolization (TACE). The recovery of phenacetin's urinary metabolites was studies in 12 normal subjects and 14 patients with HCC. Results: Compared with normal controls, the recovery of phenacetin O-de-ethylated metabolites decreased by 42·5% (P < 0·01) in patients with HCC and diminished further after TACE (P < 0·05). The ratio of plasma total paracetamol to phenacetin was much lower than in normal controls (P < 0·01) and was reduced by 40·7% more after TACE (P < 0·05). Conclusions: The metabolism of phenacetin is impaired in patient with HCC. TACE damages the activity of CYP1A2. The phenacetin test can be used to predict effect of TACE on liver function in HCC patients.
•2L tislelizumab for advanced/metastatic ESCC prolonged OS versus chemotherapy in a Europe/North America subgroup.•Tislelizumab had a more favorable safety profile versus chemotherapy in the Europe/North America patient subgroup.•Tislelizumab's efficacy and safety in the Europe/North America subgroup were consistent with the overall trial population.•Results support the potential for tislelizumab to become a 2L option for advanced ESCC in Western countries. BackgroundThe phase III RATIONALE-302 study evaluated tislelizumab, an anti-programmed cell death protein 1 antibody, as second-line (2L) treatment for advanced/metastatic esophageal squamous cell carcinoma (ESCC). This prespecified exploratory analysis investigated outcomes in patients from Europe and North America (Europe/North America subgroup).Patients and methodsPatients with tumor progression during/after first-line systemic treatment were randomized 1 : 1 to open-label tislelizumab or investigator's choice of chemotherapy (paclitaxel, docetaxel, or irinotecan).ResultsThe Europe/North America subgroup comprised 108 patients (tislelizumab: n = 55; chemotherapy: n = 53). Overall survival (OS) was prolonged with tislelizumab versus chemotherapy (median: 11.2 versus 6.3 months), with a hazard ratio (HR) of 0.55 [95% confidence interval (CI) 0.35-0.87]; HR was similar irrespective of programmed death-ligand 1 score [≥10%: 0.47 (95% CI 0.18-1.21); <10%: 0.55 (95% CI 0.30-1.01)]. Median progression-free survival was 2.3 versus 2.7 months with tislelizumab versus chemotherapy [HR: 0.97 (95% CI 0.64-1.47)]. Overall response rate was greater with tislelizumab (20.0%) versus chemotherapy (11.3%), with more durable response (median duration of response: 5.1 versus 2.1 months). Tislelizumab had a favorable safety profile versus chemotherapy, with fewer patients experiencing ≥grade 3 treatment-related adverse events (13.0% versus 51.0%). Those on tislelizumab experienced less deterioration in health-related quality of life, physical functioning, and/or disease- and treatment-related symptoms (i.e. fatigue, pain, and eating problems) as compared to those on chemotherapy, per the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) and QLQ-OES18 scores.ConclusionsAs a 2L therapy for advanced/metastatic ESCC, tislelizumab improved OS and had a favorable safety profile as compared to chemotherapy in European/North American ESCC patients in the randomized phase III RATIONALE-302 study. The phase III RATIONALE-302 study evaluated tislelizumab, an anti-programmed cell death protein 1 antibody, as second-line (2L) treatment for advanced/metastatic esophageal squamous cell carcinoma (ESCC). This prespecified exploratory analysis investigated outcomes in patients from Europe and North America (Europe/North America subgroup). Patients with tumor progression during/after first-line systemic treatment were randomized 1 : 1 to open-label tislelizumab or investigator's choice of chemotherapy (paclitaxel, docetaxel, or irinotecan). The Europe/North America subgroup comprised 108 patients (tislelizumab: n = 55; chemotherapy: n = 53). Overall survival (OS) was prolonged with tislelizumab versus chemotherapy (median: 11.2 versus 6.3 months), with a hazard ratio (HR) of 0.55 [95% confidence interval (CI) 0.35-0.87]; HR was similar irrespective of programmed death-ligand 1 score [≥10%: 0.47 (95% CI 0.18-1.21); <10%: 0.55 (95% CI 0.30-1.01)]. Median progression-free survival was 2.3 versus 2.7 months with tislelizumab versus chemotherapy [HR: 0.97 (95% CI 0.64-1.47)]. Overall response rate was greater with tislelizumab (20.0%) versus chemotherapy (11.3%), with more durable response (median duration of response: 5.1 versus 2.1 months). Tislelizumab had a favorable safety profile versus chemotherapy, with fewer patients experiencing ≥grade 3 treatment-related adverse events (13.0% versus 51.0%). Those on tislelizumab experienced less deterioration in health-related quality of life, physical functioning, and/or disease- and treatment-related symptoms (i.e. fatigue, pain, and eating problems) as compared to those on chemotherapy, per the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) and QLQ-OES18 scores. As a 2L therapy for advanced/metastatic ESCC, tislelizumab improved OS and had a favorable safety profile as compared to chemotherapy in European/North American ESCC patients in the randomized phase III RATIONALE-302 study.
e16176 Background: Hepatic artery infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs, a triplet regimen) has shown promising results in advanced hepatocellular carcinoma (HCC); however, the real world outcomes for pts with portal vein tumor thrombosis (PVTT) need further clarification. This study aimed to investigate the effectiveness of the triplet regimen in HCC pts with PVTT. Methods: We retrospectively included pts who received HAIC plus anti-PD-1 antibodies, bevacizumab or lenvatinib as first-line therapy for HCC pts with PVTT between Apr 2021 and Dec 2022. Pts received HAIC of mFOLFOX (oxaliplatin, 85 mg/m 2 ; leucovorin, 400 mg/m 2 ; 5-fluorouracil bolus, 400 mg/m 2 on day 1; 5-fluorouracil infusion, 2400 mg/m 2 for 46 h). The combination of TKIs and ICIs included 6 patterns: tislelizumab and lenvatinib (TIS-LEN), sintilimab and lenvatinib (SIN-LEN), pembrolizumab and lenvatinib (PEM-LEM), camrelizumab and lenvatinib (CAM-LEN), sintilimab and bevacizumab (SIN-BEV), and atezolizumab and bevacizumab (ATE-BEV). Primary endpoint was overall survival (OS), and secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. Results: A total of 113 pts were included, with a median age of 55 years (range 48-60). Pts characteristics were as follows: male (90.3%), hepatitis B (81.4%), BCLC C stage (100%), Child-Pugh A (92.9%), tumor number [ = 1 (45.1%), = 2 (10.6%), ≥3 (44.3%)], tumor diameter>10 cm (43.4%), extrahepatic metastasis (19.5%), beyond up to steven status (88.5%). Specific treatment options are as follows: HAIC-TIS-LEN (n = 57), HAIC-SIN-LEN (n = 21), HAIC-PEM-LEM (n = 6), HAIC-CAM-LEN (n = 12), HAIC-SIN-BEV (n = 14), and HAIC-ATE-BEV (n = 3). As of Dec 31, 2023, the median follow-up duration was 18.4 mo (95% CI, 16.7-25.1), and the median number of HAIC was 2.5 (range 2-3). The median PFS was 8.1 months (95% CI, 6.8-9.8), while the median OS reached 17.7 months (95% CI:14.5-27.6). ORR was 51.3% (3 CR, 55PR), DCR was 91.2% per RECIST 1.1; ORR was 64.6% (18 CR, 55 PR), DCR was 92% per mRECIST. 15 pts (13.3%) received surgical treatment after conversion, 13 of whom remains tumor-free to date. Among those who develop disease progression, 35.3% pts (29/83) underwent a subsequent regimen that included TACE. The most common TRAEs were hypoalbuminemia (41.6%), abdominal pain (36.3%), anorexia (33.6%), hypertension (27.4%) and hypothyroidism (25.6%). The most common grade 3-4 TRAEs included hypertension (10.6%), leukocytes count decreased (9.7%), abdominal pain (8.8%), proteinuria (6.2%) and hypoalbuminemia (5.3%). Conclusions: This study further demonstrates the clinical benefit of HAIC plus ICIs and TKIs for HCC pts with PVTT. In the future, prospective studies are warranted.
Esophageal squamous cell carcinoma (ESCC) is a common malignancy, characterized by a multistep pathogenic process regulated spatiotemporally within the esophageal epithelial microenvironment, including vessel normalization and immune infiltration. However, empirical evidence elucidating esophageal vascular remodeling and immune infiltration during ESCC tumorigenesis in situ is lacking. In this study, utilizing a mouse model recapitulating progressive human ESCC stages, we established a tissue clearing workflow for three-dimensional visualization and analysis of esophageal vessels and T cell distribution. Through this workflow, we delineated the spatial dynamics of vascular remodeling, CD3+ T cells, and characteristic T cell aggregates employing high-resolution light-sheet fluorescence microscopy across five ESCC pathogenic stages. Vessel remodeling might be coupled with T cell infiltration, and their interactions predominantly occurred at the inflammatory stage. These findings provided insights into research methodologies of esophageal cancer and spatiotemporal landscapes of vascular and T cell during ESCC initiation and progression.
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